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Elevated Circulating CD40L Concentrations in Patients with Systemic Sclerosis
KAZUHIRO KOMURA, SHINICHI SATO, MINORU HASEGAWA, MANABU FUJIMOTO, and KAZUHIKO TAKEHARA
ABSTRACT. Objective. B cell activation, fibrosis, and expression of adhesion molecules on endothelial cells are regulated by soluble CD40L (sCD40L)/CD40 interactions. Since these effects are characteristic in patients with systemic sclerosis (SSc), serum concentrations of sCD40L were determined in patients with SSc. Methods. Fifty-two Japanese patients with SSc were examined. They were grouped into 24 patients with limited cutaneous SSc (lSSc) and 28 with diffuse cutaneous SSc (dSSc). Serum sCD40L levels were examined by ELISA. As a disease control, serum samples from 20 patients with systemic lupus erythematosus (SLE) were also examined. In addition, a retrospective longitudinal study was performed in 71 serum samples from 18 patients with SSc. Results. Serum sCD40L levels were elevated in SSc patients compared with healthy controls (p < 0.001). Levels of sCD40L in patients with SSc were higher than in patients with SLE (p < 0.001) that had elevated sCD40L levels compared with healthy controls. Among SSc subsets, there were no differences in sCD40L levels between lSSc and dSSc. sCD40L levels correlated positively with C-reactive protein levels in SSc patients (p < 0.0001, r = 0.449). In a cross-sectional study and a longitudinal study, serum sCD40L levels in dSSc patients were persistently elevated, although those in lSSc patients were temporarily elevated at the early phase of the disease process. Conclusion. Patients with SSc exhibited elevated sCD40L levels that may correlate with disease activity. These results suggest that CD40/CD40L interactions may be potential therapeutic targets in SSc. (J Rheumatol 2004;31:514-9) Key Indexing Terms:
SOLUBLE CD40L
From the Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa; and the Department of Regenerative Medicine, Research Institute, International Medical Center of Japan, Tokyo, Japan. K. Komura, MD; S. Sato, MD, PhD, Associate Professor; M. Hasegawa, MD, PhD; K. Takehara, MD, PhD, Professor, Department of Dermatology, Kanazawa University Graduate School of Medical Science; M. Fujimoto, MD, PhD, Department of Regenerative Medicine, Research Institute, International Medical Center of Japan. Address reprint requests to Dr. S. Sato, Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. E-mail: s-sato@med.kanazawa-u.ac.jp Received February 17, 2003; revision accepted August 28, 2003. |